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Keywords = biologically active

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14 pages, 824 KB  
Article
Selective Extraction of Lipophilic Bioactive Compounds from Industrial Root Meal of Glycyrrhiza glabra L.
by Akbar Sanoev, Bakhodir Okhundedaev, Ildar Sham’yanov, Khayrulla Bobakulov, Sayyora Zaripova, Ruzali Botirov, Alimjan Sadikov, Shamansur Sagdullayev, Farida Ali and Eldar Garayev
Molecules 2026, 31(14), 2411; https://doi.org/10.3390/molecules31142411 - 8 Jul 2026
Abstract
Licorice (Glycyrrhiza glabra L.) root meal generated after industrial extraction of water-soluble constituents represents an underutilized secondary plant resource rich in lipophilic bioactive compounds. In this study, an efficient approach for the comprehensive recovery of hydrophobic biologically active substances from licorice root [...] Read more.
Licorice (Glycyrrhiza glabra L.) root meal generated after industrial extraction of water-soluble constituents represents an underutilized secondary plant resource rich in lipophilic bioactive compounds. In this study, an efficient approach for the comprehensive recovery of hydrophobic biologically active substances from licorice root meal was developed. The method is based on sequential ethanol extraction followed by selective fractionation using a petroleum ether–ethyl acetate solvent system and chromatographic purification. As a result, a lipid fraction (1.1%) containing phytosterols (β-sitosterol and stigmasterol) was obtained, while the pharmacologically important isoflavan glabridin was isolated with a purity of 87.9% and a yield of 0.17%. In addition, triterpenoid aglycones, including 3-oxoglycyrrhetinic acid (0.39%) and glycyrrhetinic acid (0.21%), were successfully isolated and structurally confirmed by IR and NMR spectroscopy. Comparative solvent studies demonstrated that ethanol provides the highest extraction yield (7.1%) while maintaining high levels of glabridin and total flavonoids in the extracts. The results indicate that licorice root meal is a valuable secondary source of lipophilic bioactive compounds, and the proposed approach enables more efficient utilization of plant raw materials, reduction of industrial waste, and development of sustainable technologies for obtaining pharmacologically valuable compounds for pharmaceutical, cosmetic, and biomedical applications. Full article
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16 pages, 2070 KB  
Article
Modulation of Inflammatory Stress Responses by Agave potatorum Promotes Wound Healing in Diabetic Mice
by Mónica Aideé Díaz-Román, Ramiro Ríos-Gómez, Juan-José Acevedo-Fernández, Maria Yolanda Rios and A. Berenice Aguilar-Guadarrama
Stresses 2026, 6(3), 44; https://doi.org/10.3390/stresses6030044 - 8 Jul 2026
Abstract
Persistent inflammatory and metabolic stress contribute to impaired tissue repair, particularly under diabetic conditions. Agave potatorum is traditionally used in Mexico to treat inflammation and wounds; however, its safety profile and potential to modulate stress-associated biological responses remain poorly investigated. This study evaluated [...] Read more.
Persistent inflammatory and metabolic stress contribute to impaired tissue repair, particularly under diabetic conditions. Agave potatorum is traditionally used in Mexico to treat inflammation and wounds; however, its safety profile and potential to modulate stress-associated biological responses remain poorly investigated. This study evaluated the safety, anti-inflammatory, and wound-healing activities of the hydroalcoholic extract of A. potatorum and its fractions. Safety was assessed using human keratinocytes and fibroblasts, as well as an acute oral toxicity assay (OECD Guideline 420) in female CD-1 mice. Anti-inflammatory activity was evaluated using a TPA-induced ear edema model, while wound-healing activity was assessed in normoglycemic and alloxan-induced diabetic male CD-1 mice. The hydroalcoholic extract exhibited a favorable safety profile, showing low cytotoxicity at therapeutically relevant concentrations and no signs of systemic toxicity at 2000 mg/kg. The hydroalcoholic extract and its EtOAc and n-BuOH fractions significantly reduced TPA-induced ear edema. The n-BuOH fraction also accelerated wound contraction in diabetic mice from day 6 onward, whereas only limited effects were observed in normoglycemic animals. A. potatorum exhibits a favorable preclinical safety profile and modulates biological responses associated with inflammatory stress, supporting its therapeutic potential for chronic diabetic wound healing. Full article
(This article belongs to the Section Animal and Human Stresses)
19 pages, 2967 KB  
Article
Comprehensive Changes in Phytochemical and Biological Activities Through the Fermentation Periods of Mul-Kimchi with Bitter Melon (Momordica charantia L.)
by Do-Yun Bang, Du-Yong Cho, Min-Ju Ahn, Hee-Yul Lee, Jong-Bin Jeong, Mu-Yeon Jang, Da-Hyun Kim, Hye-Rim Kim, Ye-Rim Jeong, Dea-Cheol Son and Kye-Man Cho
Fermentation 2026, 12(7), 328; https://doi.org/10.3390/fermentation12070328 - 8 Jul 2026
Abstract
Bitter melon (BM; Momordica charantia L.) is rich in phytochemicals and has been widely studied for its pharmacological effects. However, BM is mainly consumed as a tea, and its application in fermented foods remains limited. This study investigated changes in phenolic compounds, bioactive [...] Read more.
Bitter melon (BM; Momordica charantia L.) is rich in phytochemicals and has been widely studied for its pharmacological effects. However, BM is mainly consumed as a tea, and its application in fermented foods remains limited. This study investigated changes in phenolic compounds, bioactive metabolites, antioxidant and enzyme inhibitory activities, and DNA-protective effects in mul-kimchi with bitter melon (MKBM). MKBM was prepared with different BM concentrations (0%, 10%, and 20%) and fermented for 0–12 days. The phenolic profile changed according to BM concentration and fermentation periods. Epicatechin and epigallocatechin gallate were detected from day 3 only in BM-treated groups (MKBM-10 and MKBM-20). On day 12, catechin was detected only in MKBM-20, reaching 64.42 μg/mL, whereas it was not detected in MKBM-0. MKBM-20 also showed the highest total phenolic and flavonoid contents on day 12. Antioxidant and digestive enzyme inhibitory activities increased during fermentation, and DNA protection against oxidative damage was enhanced by day 9. These results suggest that mul-kimchi fermentation can improve the functional potential of BM as a fermented food ingredient. Full article
(This article belongs to the Special Issue Bioactive Compounds and Functional Properties of Fermented Foods)
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27 pages, 3959 KB  
Article
Synthesis, Biological Evaluation, Molecular Docking and Molecular Dynamics of Substituted Thieno[2,3-d]pyrimidine Derivatives as Potential Anti-Alzheimer Agents
by Asma K. Alshamari, Nourhan Magdy, Ebtesam A. Basiony, Nasser A. Hassan, Odeh A. O. Alshammari, Adel A.-H. Abdel-Rahman, Nuha O. S. Alsaif, Mona Z. Alshammari, Ahmed A. Elrashedy and Allam A. Hassan
Int. J. Mol. Sci. 2026, 27(14), 6119; https://doi.org/10.3390/ijms27146119 - 8 Jul 2026
Abstract
Thienopyrimidine derivatives are emerging as potent scaffolds for cholinesterase inhibition in Alzheimer’s disease therapy. In this work, a novel series of substituted thieno[2,3-d]pyrimidines was synthesized via Gewald’s reaction, followed by cyclization and functionalization through nucleophilic substitution and hydrazone formation. Structural confirmation was achieved [...] Read more.
Thienopyrimidine derivatives are emerging as potent scaffolds for cholinesterase inhibition in Alzheimer’s disease therapy. In this work, a novel series of substituted thieno[2,3-d]pyrimidines was synthesized via Gewald’s reaction, followed by cyclization and functionalization through nucleophilic substitution and hydrazone formation. Structural confirmation was achieved using spectroscopic techniques, and biological evaluation was performed against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with donepezil and rivastigmine as reference drugs. Compound 4 emerged as the most potent and selective AChE inhibitor (IC50 = 0.58 µM), while compound 7 also showed strong AChE inhibition (IC50 = 0.63 µM). Notably, compound 9 exhibited superior BChE inhibition (IC50 = 3.05 µM) compared to donepezil (IC50 = 8.41 µM). Dual inhibitory activity was observed for compounds 5, 6, and 11, highlighting their multitarget potential. Molecular dynamics simulations (200 ns) and MM/GBSA binding free energy calculations provided mechanistic insights. Compound 4 showed the most favorable binding energy (ΔGbind = −59.16 kcal/mol), driven by hydrogen bonds with Tyr121 and Glu199 and π-π stacking with Trp83. Residue-level decomposition identified Tyr121, Trp83, Glu199, and Tyr338 as critical contributors to binding stability. Structure–activity relationship analysis confirmed that nitrogen-containing substituents and cyclic amino moieties enhance potency, whereas bulky aromatic groups reduce activity. These findings establish thieno[2,3-d]pyrimidine derivatives as promising candidates for the development of next-generation anti-Alzheimer agents. Full article
(This article belongs to the Special Issue Research in Alzheimer’s Disease: Advances and Perspectives)
34 pages, 839 KB  
Review
An Overview of the Phytochemistry, Biological Activities and Therapeutic Potential of Epimedium spp.
by Ariana-Simina Friș, Irina Lazarova, Maya Georgieva, Loredana Gabriela Stana, Roxana Folescu, Ioana Zinuca Magyari-Pavel, Melania Munteanu and Corina Danciu
Plants 2026, 15(14), 2114; https://doi.org/10.3390/plants15142114 - 8 Jul 2026
Abstract
The genus Epimedium L. comprises a group of perennial herbs widely distributed across East Asia, with five representative species that include Epimedium grandiflorum C. Morren, Epimedium brevicornu Maxim., Epimedium sagittatum (Sieb. et Zucc.) Maxim., Epimedium koreanum Nakai. and Epimedium pubescens Maxim. For centuries, [...] Read more.
The genus Epimedium L. comprises a group of perennial herbs widely distributed across East Asia, with five representative species that include Epimedium grandiflorum C. Morren, Epimedium brevicornu Maxim., Epimedium sagittatum (Sieb. et Zucc.) Maxim., Epimedium koreanum Nakai. and Epimedium pubescens Maxim. For centuries, these species have been used in traditional Chinese medicine for their aphrodisiac, anti-osteoporotic and estrogen-like properties in the treatment of erectile dysfunction, osteoporosis, rheumatoid arthritis and menopausal symptoms. The aim of this review is to present an extensive and updated synthesis of the phytochemistry, biological activities and therapeutic properties of these five species by examining the relationship between the phytochemical composition and their pharmacological properties. Phytochemical analyses indicate that Epimedium spp. are defined by their significant content of prenylated flavonol glycosides, including icariin, icaritin, icariside, baohuoside and epimedin A-C. Recent studies have confirmed that these compounds are responsible for the genus’ therapeutic potential. They possess a variety of effects, ranging from aphrodisiac and antioxidant properties to anti-inflammatory and immunomodulatory activities, as well as neuroprotective, cardioprotective and anticancer benefits. Although preclinical findings are increasingly compelling, robust clinical evidence is still lacking for all five species. Taken together, the data summarized here position Epimedium spp. as a valuable source of bioactive prenylated flavonoids, while underscoring that standardized methodologies and rigorous clinical trials are essential to translate this potential into validated therapeutic applications. Full article
(This article belongs to the Section Phytochemistry)
25 pages, 1694 KB  
Article
Synthesis, Characterization, DFT Calculations, Biological Evaluation, and Molecular Docking of Cd(II) and Zn(II) Schiff Base Complexes: A Green Ball-Milling Approach
by Hanan Alhussain and Rania R. Zaky
Inorganics 2026, 14(7), 182; https://doi.org/10.3390/inorganics14070182 - 8 Jul 2026
Abstract
A one-pot ball-milling chelation method was used to create Cd(II) and Zn(II) complexes of a 3-hydroxy-2-naphthoyl Schiff base derivative (H2L), which provided greater efficiency under milder reaction conditions. 1H NMR, 13C NMR, UV–Vis, IR, SEM, XRD, EDX, and elemental [...] Read more.
A one-pot ball-milling chelation method was used to create Cd(II) and Zn(II) complexes of a 3-hydroxy-2-naphthoyl Schiff base derivative (H2L), which provided greater efficiency under milder reaction conditions. 1H NMR, 13C NMR, UV–Vis, IR, SEM, XRD, EDX, and elemental studies were used to characterize the isolated solid chelates. The optimized structures were confirmed by DFT theoretical calculations, which also yielded important energetic characteristics such as EHOMO and ELUMO. The three-dimensional crystal structures of HePG-2 (PDB ID: 5EQG), MCF-7 (PDB ID: 6NM0), and HeLa (PDB ID: 5IAE) were carefully analyzed after molecular docking experiments were carried out on the formed complexes utilizing Schrödinger’s LigPrep procedure with default parameters. Finally, the antibacterial, antioxidant, DNA-binding, and cytotoxic properties of the tested solid compounds were assessed. Full article
15 pages, 934 KB  
Review
Asthma: Is It Time for Monocytes to Share the Spotlight?
by Harissios Vliagoftis and Nami Shrestha Palikhe
Cells 2026, 15(14), 1233; https://doi.org/10.3390/cells15141233 - 8 Jul 2026
Abstract
The evolving understanding of the regulation of allergic airway inflammation has offered new approaches for asthma therapy. For example, our understanding of the role of alarmins, Th2 cytokines and eosinophils has allowed the development of biologics that have revolutionized therapy for severe asthma. [...] Read more.
The evolving understanding of the regulation of allergic airway inflammation has offered new approaches for asthma therapy. For example, our understanding of the role of alarmins, Th2 cytokines and eosinophils has allowed the development of biologics that have revolutionized therapy for severe asthma. However, many questions remain and several of our patients are still not controlled with the current available therapies. Many immune cells have been implicated in asthma pathophysiology, but one cell that is missing from these studies is the monocyte. Monocytes (Mos) are bone marrow-derived cells that circulate in the blood and develop into macrophages and/or dendritic cells following migration to peripheral tissues. Macrophages (Møs) and dendritic cells have been implicated in the development and progression, of allergic airway inflammation, but also in tissue repair after inflammation. Recent studies in animal models suggest a major role for Mos in allergic airway inflammation, primarily through their ability to mediate recruitment of eosinophils and/or neutrophils to the airways. However, there is little information regarding the role of monocytes in human asthma. Here we review the literature regarding the presence and functions of peripheral blood and airway Mos in human asthma and suggest further work that needs to be done to consolidate the information on Mo functions. Studies show changes in Mo numbers and activation status in the peripheral blood of patients with asthma, changes that in many cases correlate with disease severity and/or activity. Studies also show altered phenotype of Mos present in the airways of patients with asthma. Detailed human studies need to be performed, if possible, studies that include therapeutic interventions, to allow for a full understanding of the role of Mos in asthma. Full article
(This article belongs to the Collection Allergy, Asthma and Clinical Immunology)
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14 pages, 12103 KB  
Article
Rehmanniae Radix Powder Enhances Antioxidative Capacity, Immunity, and Gut Health in Late-Phase Laying Hens
by Yunqing Guo, Botao Wang and Qingping Luo
Animals 2026, 16(14), 2122; https://doi.org/10.3390/ani16142122 - 8 Jul 2026
Abstract
Physiological function is closely linked to production performance in laying hens, especially during the late laying phase. Rehmanniae Radix powder (RRP), derived from the root of Rehmannia glutinosa Libosch., exhibits diverse biological activities. We investigated the effects of RRP on immune function in [...] Read more.
Physiological function is closely linked to production performance in laying hens, especially during the late laying phase. Rehmanniae Radix powder (RRP), derived from the root of Rehmannia glutinosa Libosch., exhibits diverse biological activities. We investigated the effects of RRP on immune function in late-phase laying hens. Antioxidant capacity, serum biochemical parameters, splenic immune function, and intestinal health were evaluated. Egg production rate in the RRP group increased by 1.39 percentage points compared with the control group, while average egg weight was not significantly different between groups. Dietary RRP supplementation elevated superoxide dismutase activity and serum albumin level. Splenic expression of immune-related factors, including J-chain, interleukin-2, and caspase-3, was upregulated to varying degrees following RRP supplementation. Helper-to-cytotoxic T-cell ratio also increased, indicating enhanced immune regulation. Intestinal tight junction protein expression was significantly upregulated in the RRP group. RRP also altered relative abundance of intestinal microbes at phylum and genus levels, decreasing Actinobacteria abundance and increasing Bacteroidota abundance. Similarly, relative abundance of Bacteroides and noank_f_norank_o_Clostridia_UG-014 was elevated. Biological function of the microbial community predictions showed that glycolysis/gluconeogenesis, alanine/aspartate/glutamate, fatty acid biosynthesis, and metabolism were upregulated, while that of the quorum-sensing pathway declined. RRP supplementation improved antioxidant status, splenic immune function, and intestinal health, thereby enhancing physiological conditions in laying hens during the late laying phase. Full article
(This article belongs to the Special Issue Novel Feed Additives for Poultry Gut Health and Microbiome Modulation)
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10 pages, 4393 KB  
Brief Report
Host–Parasite Interaction: A Rostral Spike-like Structure in the Infective Stage of Salmon Lice (Lepeophtheirus salmonis) and Its Putative Role in Sensing and Initial Attachment to the Host
by Amritha Johny
Parasitologia 2026, 6(4), 38; https://doi.org/10.3390/parasitologia6040038 - 8 Jul 2026
Abstract
Lepeophtheirus salmonis (Krøyer, 1837) represents a major biological challenge in Atlantic salmon aquaculture. Despite extensive research on salmon lice biology, host interaction, and immunomodulation, the mechanisms underlying early host recognition and attachment remain poorly understood. Microscopic examination of the infective stage revealed a [...] Read more.
Lepeophtheirus salmonis (Krøyer, 1837) represents a major biological challenge in Atlantic salmon aquaculture. Despite extensive research on salmon lice biology, host interaction, and immunomodulation, the mechanisms underlying early host recognition and attachment remain poorly understood. Microscopic examination of the infective stage revealed a previously undescribed spike-like structure in the anterior rostral region of the copepodids. The structure appeared flexible, moved synchronously with body movements, and was present prior to exposure to host tissues or detectable host contact. Behavioral observations further revealed that copepodids actively probe salmon skin explants and fins with their anterior appendages before initial attachment, often followed by prolonged immobility. Scanning electron microscopy suggested that the structure may exist in both protruded and retracted forms and revealed a crevice- or pore-like feature at its proximal end. It is hypothesized that this structure may contribute to early host interrogation through localized sensing and the initial attachment process. These findings highlight a component of early host–parasite interactions and may contribute to future strategies to disrupt host recognition mechanisms in salmon lice. Full article
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32 pages, 21033 KB  
Perspective
Targeting the Anthropocene: Advanced Bio-Systems for Global Microplastic Mitigation
by Mina Popović and Nevenka Rajić
Microplastics 2026, 5(3), 138; https://doi.org/10.3390/microplastics5030138 - 8 Jul 2026
Abstract
The global proliferation of microplastics demands sustainable remediation alternatives to energy-intensive conventional disposal methods, shifting research focus toward polymer-degrading microbial communities within the “plastisphere.” The primary objectives of this study are twofold: first, to systematically decode the sequential biophysical mechanisms underlying microplastic colonization [...] Read more.
The global proliferation of microplastics demands sustainable remediation alternatives to energy-intensive conventional disposal methods, shifting research focus toward polymer-degrading microbial communities within the “plastisphere.” The primary objectives of this study are twofold: first, to systematically decode the sequential biophysical mechanisms underlying microplastic colonization and enzymatic degradation; and second, to establish an empirically validated, scalable treatment framework that employs both a novel biological isolate and a hybrid engineering architecture. Experimentally, we investigate the multi-stage colonization process and demonstrate that “Phase Zero” conditioning films modulate the surface zeta potential (ζ) to anchor pioneer r-strategists. To evaluate degradative efficacy under accelerated conditions without abiotic pretreatment, the newly isolated carp gut strain Hafnia paralvei UUNT_MP29 was exposed to pristine low-density polyethylene (LDPE) and polystyrene (PS). Over a 16-day biotic incubation period, structural and chemical alterations were distinctly polymer-specific: bacterial action on the polyolefin LDPE yielded a Carbonyl Index of 0.4594 and a 10.95 °C reduction in thermal stability (Tmax), whereas the aromatic PS matrix exhibited a Carbonyl Index of 0.3235 alongside a 10.80 °C decrease in Tmax, with both substrates showing intense surface pitting. To standardize these complex tracking metrics across the field, a universal four-pillar Biodegradability Index (BI) was formulated. Based on these findings, we recommend an immediate transition from passive waste containment to a closed-loop engineering approach. Specifically, we propose integrating an artificial intelligence (AI)-managed hybrid bioprocess configuration that couples Advanced Oxidation Processes (AOPs) with Membrane Bioreactors (MBRs). This dual-stage configuration is recommended to overcome polyolefin crystallinity, accelerate stoichiometric mineralization, and actively mitigate additive-mediated toxicity at the industrial scale, providing a vital blueprint for the circular bio-economy. Full article
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34 pages, 5158 KB  
Article
Phytochemical Characterisation and Skin-Relevant In Vitro Biological Activity of Leaf Extracts from Selected Geranium Species
by Maciej Książkiewicz, Emil Paluch, Jarosław Widelski, Justyna Stefanowicz-Hajduk, Kinga Kochan-Jamrozy, Olga Bortkiewicz, Krzysztof Kamil Wojtanowski, Magdalena Gucwa, Judyta Cielecka-Piontek and Elżbieta Studzińska-Sroka
Molecules 2026, 31(14), 2406; https://doi.org/10.3390/molecules31142406 - 8 Jul 2026
Abstract
In the search for natural compounds with skin-relevant biological activity, the leaves from three species of the Geraniaceae family (Geranium phaeum, Geranium sanguineum, and Geranium macrorrhizum) were investigated. The study combined phytochemical characterisation with a broad evaluation of biological [...] Read more.
In the search for natural compounds with skin-relevant biological activity, the leaves from three species of the Geraniaceae family (Geranium phaeum, Geranium sanguineum, and Geranium macrorrhizum) were investigated. The study combined phytochemical characterisation with a broad evaluation of biological activity. The bioactivity of the tested extracts was assessed using antioxidant assays (DPPH, ABTS, and CUPRAC), metal-chelating tests, and inhibition assays of hyaluronidase, elastase, and tyrosinase. In addition, antimicrobial activity was evaluated against selected Gram-positive and Gram-negative bacteria and Candida spp., while cytocompatibility was assessed using HaCaT keratinocytes and HFF-1 fibroblasts. To support the interpretation of the observed biological effects, qualitative phytochemical profiling of the extracts was performed by LC–MS; selected compounds were quantified by HPLC; and total polyphenol and flavonoid contents (TPC and TFC) were determined. Overall, the extracts exhibited notable antioxidant, antimicrobial, and enzyme-inhibitory activities, while maintaining good cytocompatibility at lower concentrations. Among the tested species, G. sanguineum and G. macrorrhizum showed the most pronounced overall activity, likely associated with their high polyphenol content. These results indicate that selected Geraniaceae species represent promising sources of bioactive compounds with combined antioxidant, antimicrobial, and skin-compatible properties, supporting their further investigation in skin-relevant in vitro and formulation-oriented studies. Full article
(This article belongs to the Special Issue Biological Evaluation of Plant Extracts, 2nd Edition)
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23 pages, 8627 KB  
Article
Extraction and Purification of Polysaccharides from Thermotolerant Pyropia haitanensis Strain SW-81 and Its Hypolipidemic Effects on Oleic Acid-Induced Lipid Accumulation in HepG2 Cells
by Jiawei Zhong, Hongchang Ding, Jogeir Toppe, Kaiyue Chen, Menghan Wei, Xin Chen, Long Zhang, Quancai Sun, Ye Peng, Wenhui Wu, Wanqiang Wu and Xichang Wang
Mar. Drugs 2026, 24(7), 241; https://doi.org/10.3390/md24070241 - 8 Jul 2026
Abstract
Pyropia haitanensis polysaccharides have attracted growing attention for their diverse biological activities. In this study, we developed a synergistic extraction approach combining ultrasonic-assisted treatment and enzymatic hydrolysis using cellulase and pectinase. Response surface methodology (RSM) was applied to optimize the extraction conditions, which [...] Read more.
Pyropia haitanensis polysaccharides have attracted growing attention for their diverse biological activities. In this study, we developed a synergistic extraction approach combining ultrasonic-assisted treatment and enzymatic hydrolysis using cellulase and pectinase. Response surface methodology (RSM) was applied to optimize the extraction conditions, which were determined as follows: 1.48% cellulase, 1.47% pectinase, 180 W ultrasonic power, and 65.9 °C temperature. Under these conditions, the polysaccharide yield reached 10.184 ± 0.27%. The crude extract was then purified through sequential DEAE Sepharose FastFlow and Sephadex G-75 chromatography, resulting in the purified fraction PPHP3. Monosaccharide analysis revealed that galactose, glucose, and glucuronic acid constituted the primary components in a molar ratio of 98.3:0.46:1.24. This polysaccharide exhibited a weight-average molecular weight of 25.208 kDa, a sulfate content of 8.64 ± 0.05%. In hypolipidemic assays using oleic acid-induced HepG2 cells, PPHP3 significantly reduced intracellular triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C), while simultaneously increasing HDL-C levels. These findings highlight the potential of P. haitanensis polysaccharides for hypolipidemic applications and establish a scientific foundation for their development in therapeutic and practical contexts. Full article
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16 pages, 2035 KB  
Article
Nanog+F10-Derived Extracellular Vesicles Suppress Melanoma Metastasis, Implicating miR-19a-3p in Macrophage-Dependent Innate Immune Regulation
by Misato Nakano, Asuka Tamura, Sora Yorikawa, Nahoko Matsuki, Runa Ito, Hideaki Matsuoka and Mikako Saito
Cancers 2026, 18(14), 2200; https://doi.org/10.3390/cancers18142200 - 8 Jul 2026
Abstract
Background/Objectives: Extracellular vesicles (EVs) participate in tumor progression and immune regulation through the transfer of bioactive molecules. Although tumor-derived EVs are generally considered to promote metastasis, accumulating evidence suggests that their functions vary according to the biological characteristics of their cells of origin. [...] Read more.
Background/Objectives: Extracellular vesicles (EVs) participate in tumor progression and immune regulation through the transfer of bioactive molecules. Although tumor-derived EVs are generally considered to promote metastasis, accumulating evidence suggests that their functions vary according to the biological characteristics of their cells of origin. This study investigated the mechanisms underlying the anti-metastatic effects of EVs derived from Nanog-overexpressing melanoma cells (Nanog+F10-EVs). Methods: Nanog+F10-EVs were isolated and characterized by EV marker expression. Their anti-metastatic activity was evaluated using melanoma liver metastasis models in Rag2-deficient and macrophage-depleted mice. Differential miRNA expression analysis was performed to identify candidate functional mediators. Functional studies were conducted using miR-19a-3p-overexpressing cells and EVs. Results: Nanog+F10-EVs significantly suppressed melanoma metastasis. Rag2 deficiency only modestly affected this activity, whereas macrophage depletion abolished the anti-metastatic effect, suggesting a predominant role of innate immunity. miRNA profiling identified miR-19a-3p as a candidate mediator enriched in Nanog+F10-EVs. Despite promoting tumor cell proliferation and migration, miR-19a-3p-enriched EVs partially reproduced anti-metastatic activity. Macrophage marker analysis suggested that these effects were not fully explained by classical M1/M2 polarization. Conclusions: Nanog+F10-EVs may suppress metastasis through macrophage-dependent innate immune regulation potentially mediated by miR-19a-3p and are consistent with a model of preemptive immune education. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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19 pages, 1557 KB  
Review
Temporal Hierarchy of Hydrogels and Orthobiologic Therapies for Knee Osteoarthritis
by Fábio Ramos Costa, Rubens Martins, João Protásio Netto, Vinicius Calumby Costa, Gabriel Azzini, André Kruel, Tomas Mosaner, Lucas Furtado da Fonseca and José Fábio Lana
Gels 2026, 12(7), 608; https://doi.org/10.3390/gels12070608 - 8 Jul 2026
Abstract
Knee osteoarthritis is commonly managed with intra-articular therapies that differ widely in composition, mechanism, and clinical persistence, yet the duration of their benefit is discussed inconsistently, which limits practical comparison between ozone, hyaluronic acid, platelet-derived products, and cell-rich orthobiologics. In this narrative review [...] Read more.
Knee osteoarthritis is commonly managed with intra-articular therapies that differ widely in composition, mechanism, and clinical persistence, yet the duration of their benefit is discussed inconsistently, which limits practical comparison between ozone, hyaluronic acid, platelet-derived products, and cell-rich orthobiologics. In this narrative review we examine the mechanism-driven temporal behavior of these therapies, focusing on the physicochemical, biomechanical, biological, and regenerative factors that influence how long a clinical response persists. By temporal hierarchy we mean the mechanistically informed pattern by which therapies differ in the duration of their physicochemical presence, biological activity, and clinical benefit, not a ranking of efficacy or a claim of equivalence. Read against this definition, ozone occupies the shortest end of the spectrum; conventional hyaluronic acid shows intermediate persistence; modified hyaluronic acid hydrogels may extend activity through improved rheology and enzymatic resistance; platelet-rich plasma and injectable platelet-rich fibrin provide more sustained biological signaling; and bone marrow aspirate concentrate and stromal vascular fraction may act over longer periods through trophic and paracrine pathways. Heterogeneity in study design, patient selection, and outcome reporting still limits firm conclusions, and standardized reporting of product characteristics and time-related endpoints will be essential to validate or refine the proposed framework. Full article
(This article belongs to the Section Gel Analysis and Characterization)
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24 pages, 2645 KB  
Article
Organic Germanium (Ge-132) Reduces Glycative Damage While Maintaining Cellular Stress Signaling, Revealing Limited Coordination Between Biochemical and Cellular Responses
by Yasin Fauzi Ahmed El-Adhiri, Gabrielle Guillamin, Amanda Martell Vergara, Lucia Gimeno Mallech and Antonella Locascio
Molecules 2026, 31(14), 2405; https://doi.org/10.3390/molecules31142405 - 8 Jul 2026
Abstract
Organogermanium compounds, particularly carboxyethyl germanium sesquioxide (Ge-132), have been studied for decades because of their diverse biological effects, especially their antioxidant properties. However, the available literature remains fragmented and highly heterogeneous, which limits mechanistic interpretation. Although antiglycative activity has been described at the [...] Read more.
Organogermanium compounds, particularly carboxyethyl germanium sesquioxide (Ge-132), have been studied for decades because of their diverse biological effects, especially their antioxidant properties. However, the available literature remains fragmented and highly heterogeneous, which limits mechanistic interpretation. Although antiglycative activity has been described at the biochemical level, the downstream transcriptional effects of Ge-132 under glycative stress remain poorly characterized. Here, we combined an evidence-mapping analysis with targeted molecular analysis in a standardized cellular model to examine whether the antiglycative effects of Ge-132 are accompanied by coordinated transcriptional responses. The mapping guided selection of markers associated with glycative stress, including carbonyl detoxification, redox adaptation, autophagy, lysosomal function, and inflammatory signaling. Gene expression analysis revealed limited and selective transcriptional modulation under glycative stress conditions. In parallel, protein analysis showed reduced intracellular accumulation of advanced glycation end products (AGEs) in Ge-132–treated. These findings suggest that reduction of glycative damage can occur without proportional transcriptional activation of stress-response pathways under the conditions tested. However, alternative explanations, such as model constraints, acute exposure duration, or limited gene panel sensitivity, cannot be excluded. Full article
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